Results of the monarchE study showed patients with hormone receptor–positive (HR+), HER2-negative (HER2–) high-risk, early breast cancer had greater benefit after 5 years when receiving adjuvant abemaciclib plus endocrine therapy vs endocrine therapy alone.
Patients with hormone receptor–positive, HER2-negative (HER2–) high-risk breast cancer have a high risk of recurrence of up to 30% in 5 years. However, the latest results of the monarchE study evaluating adjuvant abemaciclib (Verzenio) plus endocrine therapy vs endocrine therapy alone found fewer deaths and lower rates of invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) for the patients receiving abemaciclib at 5 years.
The results were presented at ESMO Congress 2023 by Nadia Harbeck, MD, PhD, head of the Breast Center at the LMU University Hospital in Munich, Germany.
The study design included 91% of patients in cohort 1, which was a group of high-risk patients based on clinical pathological features, and 9% of patients in cohort 2, which were high-risk patients based on the Ki-67 gene. The cutoff for high-risk based on the Ki-67 gene was ≥ 20%. The entire intention-to-treat (ITT) population was both cohorts combined. A total of 5637 patients were randomized in a 1:1 fashion to either abemaciclib plus endocrine therapy or endocrine therapy alone.
The presented results had a cutoff date of July 3, 2023. The median follow up was 54 months. All of the patients received therapy for 2 years and are now off abemaciclib. More than 80% of the patients have follow-up of at least 2 years since completing abemaciclib.
At 5 years, the monarchE trial showed a sustained IDFS benefit in the ITT population, Harbeck said. The absolute difference between IDFS rates between the 2 arms was 7.6% at 5 years. The abemaciclib arm had a 32% reduction of developing an IDFS event (HR, 0.680; 95% CI; 0.599-0.772; P < .001).
Importantly, the IDFS benefit was consistent across clinically relevant subgroups independent of age, menopausal status, type or setting of chemotherapy give, and number of positive nodes, Harbeck said.
The ITT population also showed a sustained DRFS rate survival benefit with an absolute difference between the 2 arms of 6.7% at 5 years and a 32.5% reduction in the risk of developing a DRFS event (HR, 0.675; 95% CI, 0.588-0.774; P < .001).
There was no statistical significance between the 2 arms for overall survival, although there was some separation between the curves starting to happen later in the follow-up period.
“Overall survival [data] are still immature, which I think is great for patients, so they do have years to come even after distant recurrences,” Harbeck said. “I think this is good news.”
There was a numerical difference in deaths due to breast cancer, with fewer in the abemaciclib arm compared with the endocrine alone arm. However, there was no substantial difference in deaths not related to breast cancer.
The data on treatment benefit from cohort 1 was consistent with the ITT population; however, the data from cohort 2 remains immature because that group started a year later. For cohort 2, there were similar abemaciclib treatment effects regardless of Ki-67 index.
“I think it’s astounding that Ki-67, even in such a high-risk population of node-positive, early[-stage] breast cancer patients is a prognostic factor,” Harbeck said. “We can see that the absolute values for the survival rates are lower in the high Ki-67 group.”
There were no new safety results in the trial. With all the patients having completed treatment, Harbeck viewed it as reassuring that the serious adverse events reported in the follow-up period were similar between the abemaciclib and endocrine alone groups.
“In conclusion, the data are consistent with a carryover effect and further support the addition of adjuvant abemaciclib to endocrine therapy for patients with hormone receptor–positive, HER2-negative, node-positive, high-risk early breast cancer,” Harbeck said.